This invention relates to 1-sulfonyl-4-aminoalkoxy indole derivatives, and associated compositions, methods for use as therapeutic agents, and methods of preparation thereof.
The actions of the neurotransmitter 5-hydroxytryptamine (5-HT) as a major modulatory neurotransmitter in the brain, are mediated through a number of receptor families termed 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7. Based on a high level of 5-HT6 receptor mRNA in the brain, it has been stated that the 5-HT6 receptor may play a role in the pathology and treatment of central nerve system disorders. In particular, 5-HT6 selective ligands have been identified as potentially useful in the treatment of certain CNS disorders such as Parkinson""s disease, Huntington""s disease, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, migraine, Alzheimer""s disease (enhancement of cognitive memory), sleep disorders, feeding disorders such as anorexia and bulimia, panic attacks, attention deficit hyperactivity disorder (ADHD), attention deficit disorder (ADD), withdrawal from drug abuse such as cocaine, ethanol, nicotine and benzodiazepines, schizophrenia, and also disorders associated with spinal trauma and/or head injury such as hydrocephalus. Such compounds are also expected to be of use in the treatment of certain gastrointestinal (GI) disorders such as functional bowel disorder. See for example, B. L. Roth et al., J. Pharmacol. Exp. Ther., 1994, 268, pages 1403-14120, D. R. Sibley et al., Mol. Pharmacol., 1993, 43, 320-327, A. J. Sleight et al., Neurotransmission, 1995, 11, 1-5, and A. J. Sleight et al., Serotonin ID Research Alert, 1997, 2(3), 115-8. 5-HT6 antagonists have also been identified as potentially useful compounds for treatment of obesity. See for example, Bentley et al., Br. J. Pharmac. 1999, Suppl 126; Bently et al., J. Psychopharmacol. 1997, Suppl A64: 255; Wooley et al., Neuropharmacology 2001, 41: 210-129; and WO 02/098878.
While some 5-HT6 modulators have been disclosed, there continues to be a need for compounds that are useful for modulating 5-HT6.
The present invention provides a compound of the formula: 
a pharmaceutically acceptable salt or a prodrug thereof,
wherein
n is 2 or 3;
each of R1 and R2 is independently hydrogen, lower alkyl, or R1 and R2 together with the nitrogen atom to which they are attached may form a heterocyclyl group;
each R3 is independently hydrogen or alkyl, or R3 and R1 together with the nitrogen atom to which R1 is attached may form a four to seven membered ring moiety with R1 and R3 together forming an alkylene group;
R4 is hydrogen, lower alkyl, or haloalkyl;
R5 is hydrogen, lower alkyl, halo, alkoxy, or haloalkyl; and
R6 is optionally substituted aryl or optionally substituted heteroaryl.
The present invention also provides methods for preparing, compositions comprising, and methods for using Compounds of Formula I.